Identification of a novel macrophage population in the normal mouse corneal stroma.

Purpose: To examine the normal murine corneal stroma for the presence of bone marrow-derived leukocytes.

Methods: Wholemounts of paraformaldehyde-fixed corneal stroma from normal mice at 5 to 16 weeks of age were examined in single- and double-color immunomorphologic studies performed with confocal microscopy. The phenotype, morphology, distribution, and density of immunopositive cells were determined.

Flt-3 ligand (FL) drives differentiation of rat bone marrow-derived dendritic cells expressing OX62 and/or CD161 (NKR-P1).

Bone marrow-derived dendritic cells (DC) of the rat have not been as well characterized as those from the mouse. Here, large quantities of bone marrow-derived rat DC were generated when Flt-3 ligand (FL) was used as an adjunct to granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). These cells displayed a typical DC phenotype, expressing MHC class II, CD54, CD80, CD86, and CD11b/c.

Immunization with an antigen identified by cytokine tumor vaccine-assisted SEREX (CAS) suppressed growth of the rat 9L glioma in vivo.

We have reported previously that s.c. immunization of rats with IL-4 transduced 9L gliosarcoma cells (9L-IL-4) induced a potent antitumor immunity against intracranial, parental 9L tumors.

Cytokine gene therapy of gliomas: induction of reactive CD4+ T cells by interleukin-4-transfected 9L gliosarcoma is essential for protective immunity.

Tumor cells genetically modified to secrete cytokines stimulate potent immune responses against peripheral and central nervous system tumors; however, variable results on the efficacy of this strategy for therapeutic intervention against established intracranial neoplasia have been reported. We have found that vaccination with rat 9L gliosarcoma cells expressing interleukin 4 (9LmIL4) induced a specific, protective, immune response against rechallenge with parental 9L tumors. In naive rats, sham-transfected 9L (9Lneo) tumors and 9LmIL4 tumors grew at comparable rates for 12-14 days, and then 9LmIL4 tumors regressed.

Acute stress impairs NK cell adhesion and cytotoxicity through CD2, but not LFA-1.

Using a nonhuman primate model, we examined the mechanisms by which acute social stress inhibits the ability of NK cells to form conjugates with, and lyse target cells. We examined the expression and role of the primary NK cell adhesion molecules, CD2 and LFA-1, in mediating conjugation to target cells. Acute stress induced a decrease in NK cell expression of CD2 (17+/-3%); and to a lesser degree induced a decrease in expression of LFA-1 (CD11a: 8+/-3%; CD18: 7+/-3%).

Selective reduction in CD2 expression on CD2bright/CD8+ lymphocytes from cynomolgus monkeys (Macaca fascicularis) in response to acute stress.

Numerous reports have demonstrated a link between stressful stimuli and immune suppression. However, the cellular mechanisms by which stress impairs immune function are largely unknown. We have examined the effects of an acute stressor on the T cell population, specifically, the number and phenotype of T cells in a nonhuman primate model.

Suppression of splenic T lymphocyte proliferation by acute cocaine administration.

We have recently demonstrated that cocaine administration has a limited effect on mitogen-stimulated T lymphocyte proliferation. The present study investigated the effect of cocaine on splenic T cell response to alloantigens. Rats received intraperitoneal injections of cocaine HCI, and splenocytes were isolated either thirty minutes or three hours post-administration.

NKR-P1dim/TCR alpha beta + T cells and natural killer cells share expression of NKR-P1A and NKR-P1D.

Natural killer (NK) cells and a T cell subset express NKR-P1s; however, it is not known if NKR-P1s on these cells are homologous. By molecular and biochemical means, we determined that NKR-P1s on NK cells and T cells were similar. Also, sequencing of polymerase chain reaction products derived from these populations indicated expression of a novel form, termed NKR-P1D, with approximately 60% nucleotide homology to NKR-P1A.

Hanging in the balance: natural killer cell recognition of target cells.

Natural killer (NK) cells kill certain tumor cells and virus-infected cells directly. Until recently, little was known about how they recognize their targets. Now, several candidate NK receptors have been identified, some of which may have carbohydrate ligands.

Characterization and comparison of the lytic function of NKR-P1+ and NKR-P1-rat natural killer cell clones established from NKR-P1bright/TCR alpha beta-cell lines.

From sorted rat NKR-P1bright/T cell receptor (TCR) alpha beta-cells, we established interleukin (IL)-2-dependent cell lines with the morphology, phenotype and function of natural killer (NK) cells. The cell lines NKbr11.3 and NKbr1.

Characterization and function of the NKR-P1dim/T cell receptor-alpha beta+ subset of rat T cells.

MHC-unrestricted cytotoxicity is mediated primarily by NK cells. However, some subsets of TCR-alpha beta+ and TCR-gamma delta+ T cells also have the capacity to mediate MHC-unrestricted cytotoxicity, particularly after incubation in high concentrations of IL-2. Currently, it is not known what receptors on T cells are responsible for this activity, nor whether such receptors are the same as those on NK cells.

Induction of HLA-specific CTL to nonimmunogenic, heat-inactivated lymphocytes by interleukin 2.

Human lymphocytes that have been heat-inactivated (1 hr, 45 degrees C) were used as stimulator cells in a model system to study the requirements of allogeneic T cell activation in vitro. Cytotoxic T lymphocytes were not generated in either primary or secondary mixed lymphocyte cultures after exposure to heated stimulator cells. Successful reconstitution of cytolytic activity in primary cultures was achieved by the addition of rIL-2.